シラメシン

シラメシン
IUPAC命名法による物質名
	IUPAC名 1'-{4-[1-(4-fluorophenyl)-1H-indol-3-yl]butyl}-3H-spiro[2-benzofuran-1,4'-piperidine];
データベースID
CAS番号;	147817-50-3
ATCコード	none
PubChem	CID: 9829526
ChemSpider	8005261
UNII	3IX8CWR24V
化学的データ
化学式	C30H31FN2O
分子量	454.59 g/mol
	SMILES C1CN(CCC12C3=CC=CC=C3CO2)CCCCC4=CN(C5=CC=CC=C54)C6=CC=C(C=C6)F;
	InChI InChI=1S/C30H31FN2O/c31-25-12-14-26(15-13-25)33-21-23(27-9-2-4-11-29(27)33)7-5-6-18-32-19-16-30(17-20-32)28-10-3-1-8-24(28)22-34-30/h1-4,8-15,21H,5-7,16-20,22H2 ; Key:XWAONOGAGZNUSF-UHFFFAOYSA-N ;
	テンプレートを表示

シラメシン（英: siramesine）は、σ2サブタイプに選択性を持つシグマ受容体アゴニストである^[1]。動物実験では、抗不安薬^[2]及び抗うつ薬^[3]の効果が示されている。不安症の治療を目的としてルンドベックが開発したが^[4]、治験によりヒトには効果がないことが判明して開発は中断した。

シラメシンは、NMDA受容体アンタゴニストと共に投与することで、抗うつ効果が増進することが示されている^[5]。また、コカインのσ2受容体に対する活性の研究にも用いられ^[6]、in vitro^[7]とin vivo^[8]の双方での抗がん作用が示されている。

出典

^ Søby, Karina Krøyer; Mikkelsen, Jens D.; Meier, Eddi; Thomsen, Christian (2002-07). “Lu 28-179 labels a sigma(2)-site in rat and human brain”. Neuropharmacology 43 (1): 95–100. doi:10.1016/s0028-3908(02)00071-0. ISSN 0028-3908. PMID 12213263.
^ Sánchez, C.; Arnt, J.; Costall, B.; Kelly, M. E.; Meier, E.; Naylor, R. J.; Perregaard, J. (1997-12-XX). “The selective sigma2-ligand Lu 28-179 has potent anxiolytic-like effects in rodents”. The Journal of Pharmacology and Experimental Therapeutics 283 (3): 1323–1332. ISSN 0022-3565. PMID 9400007.
^ Sánchez, C.; Papp, M. (2000-04). “The selective sigma2 ligand Lu 28-179 has an antidepressant-like profile in the rat chronic mild stress model of depression”. Behavioural Pharmacology 11 (2): 117–124. doi:10.1097/00008877-200004000-00003. ISSN 0955-8810. PMID 10877116.
^ Heading, C. (2001-02). “Siramesine H Lundbeck”. Current Opinion in Investigational Drugs (London, England: 2000) 2 (2): 266–270. ISSN 1472-4472. PMID 11816842.
^ Skuza, G.; Rogóz, Z. (2006-06). “The synergistic effect of selective sigma receptor agonists and uncompetitive NMDA receptor antagonists in the forced swim test in rats”. Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society 57 (2): 217–229. ISSN 0867-5910. PMID 16845227.
^ Nuwayhid, Samer J.; Werling, Linda L. (2006-03-27). “Sigma2 (sigma2) receptors as a target for cocaine action in the rat striatum”. European Journal of Pharmacology 535 (1-3): 98–103. doi:10.1016/j.ejphar.2005.12.077. ISSN 0014-2999. PMID 16480713.
^ Ostenfeld, Marie Stampe; Fehrenbacher, Nicole; Høyer-Hansen, Maria; Thomsen, Christian; Farkas, Thomas; Jäättelä, Marja (2005-10-01). “Effective tumor cell death by sigma-2 receptor ligand siramesine involves lysosomal leakage and oxidative stress”. Cancer Research 65 (19): 8975–8983. doi:10.1158/0008-5472.CAN-05-0269. ISSN 0008-5472. PMID 16204071.
^ Groth-Pedersen, Line; Ostenfeld, Marie Stampe; Høyer-Hansen, Maria; Nylandsted, Jesper; Jäättelä, Marja (2007-03-01). “Vincristine induces dramatic lysosomal changes and sensitizes cancer cells to lysosome-destabilizing siramesine”. Cancer Research 67 (5): 2217–2225. doi:10.1158/0008-5472.CAN-06-3520. ISSN 0008-5472. PMID 17332352.

外部リンク

Siramesine - MeSH・アメリカ国立医学図書館・生命科学用語シソーラス（英語）

[1] Søby, Karina Krøyer; Mikkelsen, Jens D.; Meier, Eddi; Thomsen, Christian (2002-07). “Lu 28-179 labels a sigma(2)-site in rat and human brain”. Neuropharmacology 43 (1): 95–100. doi:10.1016/s0028-3908(02)00071-0. ISSN 0028-3908. PMID 12213263.

[2] Sánchez, C.; Arnt, J.; Costall, B.; Kelly, M. E.; Meier, E.; Naylor, R. J.; Perregaard, J. (1997-12-XX). “The selective sigma2-ligand Lu 28-179 has potent anxiolytic-like effects in rodents”. The Journal of Pharmacology and Experimental Therapeutics 283 (3): 1323–1332. ISSN 0022-3565. PMID 9400007.

[3] Sánchez, C.; Papp, M. (2000-04). “The selective sigma2 ligand Lu 28-179 has an antidepressant-like profile in the rat chronic mild stress model of depression”. Behavioural Pharmacology 11 (2): 117–124. doi:10.1097/00008877-200004000-00003. ISSN 0955-8810. PMID 10877116.

[4] Heading, C. (2001-02). “Siramesine H Lundbeck”. Current Opinion in Investigational Drugs (London, England: 2000) 2 (2): 266–270. ISSN 1472-4472. PMID 11816842.

[5] Skuza, G.; Rogóz, Z. (2006-06). “The synergistic effect of selective sigma receptor agonists and uncompetitive NMDA receptor antagonists in the forced swim test in rats”. Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society 57 (2): 217–229. ISSN 0867-5910. PMID 16845227.

[6] Nuwayhid, Samer J.; Werling, Linda L. (2006-03-27). “Sigma2 (sigma2) receptors as a target for cocaine action in the rat striatum”. European Journal of Pharmacology 535 (1-3): 98–103. doi:10.1016/j.ejphar.2005.12.077. ISSN 0014-2999. PMID 16480713.

[7] Ostenfeld, Marie Stampe; Fehrenbacher, Nicole; Høyer-Hansen, Maria; Thomsen, Christian; Farkas, Thomas; Jäättelä, Marja (2005-10-01). “Effective tumor cell death by sigma-2 receptor ligand siramesine involves lysosomal leakage and oxidative stress”. Cancer Research 65 (19): 8975–8983. doi:10.1158/0008-5472.CAN-05-0269. ISSN 0008-5472. PMID 16204071.

[8] Groth-Pedersen, Line; Ostenfeld, Marie Stampe; Høyer-Hansen, Maria; Nylandsted, Jesper; Jäättelä, Marja (2007-03-01). “Vincristine induces dramatic lysosomal changes and sensitizes cancer cells to lysosome-destabilizing siramesine”. Cancer Research 67 (5): 2217–2225. doi:10.1158/0008-5472.CAN-06-3520. ISSN 0008-5472. PMID 17332352.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

IUPAC命名法による物質名

IUPAC名 1'-{4-[1-(4-fluorophenyl)-1H-indol-3-yl]butyl}-3H-spiro[2-benzofuran-1,4'-piperidine]
データベースID
CAS番号	147817-50-3
ATCコード	none
PubChem	CID: 9829526
ChemSpider	8005261
UNII	3IX8CWR24V
化学的データ
化学式	C₃₀H₃₁F N₂O
分子量	454.59 g/mol
SMILES C1CN(CCC12C3=CC=CC=C3CO2)CCCCC4=CN(C5=CC=CC=C54)C6=CC=C(C=C6)F
InChI InChI=1S/C30H31FN2O/c31-25-12-14-26(15-13-25)33-21-23(27-9-2-4-11-29(27)33)7-5-6-18-32-19-16-30(17-20-32)28-10-3-1-8-24(28)22-34-30/h1-4,8-15,21H,5-7,16-20,22H2 Key:XWAONOGAGZNUSF-UHFFFAOYSA-N
テンプレートを表示